Is INPP5E p.Phe418fs (c.1253_1256del) pathogenic?

INPP5E p.Phe418fs (c.12531256del) is classified Pathogenic in INPP5E (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-10). No gnomAD frequency available for this variant; Associated with Joubert syndrome.

What condition is associated with INPP5E p.Phe418fs (c.1253_1256del)?

INPP5E p.Phe418fs (c.1253_1256del) is associated with Joubert syndrome (ClinVar).

How common is INPP5E p.Phe418fs (c.1253_1256del) in the general population?

INPP5E p.Phe418fs (c.1253_1256del) is no gnomAD frequency available for this variant (gnomAD).

INPP5E p.Phe418fs

c.1253_1256del · rs2131608672 · VCV1070977

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Joubert syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP -1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: INPP5E
Protein: p.Phe418fs
Coding: c.1253_1256del
MANE Select: NM_019892
dbSNP: rs2131608672
Type: Microsatellite
Location: chr9:136432979 (GRCh38)
Structure: AlphaFold pLDDT 88.46

Full INPP5E gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

INPP5E c.812+7_812+10del Benign ★★ same condition
INPP5E p.Arg95dup Uncertain significance ★ same condition
INPP5E p.Thr355_Leu356insArgLeuGlnAspThr Uncertain significance ★ same condition
INPP5E c.1035-8_1035-6del Likely benign ★ same condition
INPP5E c.1159+7_1159+8insGGTGGGCGTGGCTGGAGGGGTGGGCGTGGCTGGAGGGGTGGGCGTGGCTGGAGG Likely benign ★ same condition
INPP5E c.1159+7_1159+8insGTGGCTGGAGGGGTGGGT Likely benign ★ same condition
PMPCA p.Thr418= Likely benign ★ same residue
INPP5E p.Arg378Cys Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/inpp5e-p-phe418fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown